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==Cancer Category/Type==
==Cancer Category/Type==
[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
---[http://www.ccga.io/index.php/Acute_Promyelocytic_Leukemia_(APL)_with_PML-RARA Acute Promyelocytic Leukemia (APL) with PML-RARA]
---[http://www.ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion Acute Promyelocytic Leukemia (APL) with PML-RARA]
Based on the early French-American-British (FAB) classification, Acute Promyelocytic Leukaemia (APL) is one of the subtypes (M3) of Acute Myeloid Leukemia AML [1]. The PML-RARA fusion is reportedly found in 5-15% of AML and occurs at any age but predominantly in adults in mid-life [1,2]. ''RARA'' fusion proteins behave as potent transcriptional repressors of retinoic acid signaling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of all-trans retinoic acid (ATRA) or arsenic trioxide [1-5]. ATO (arsenic trioxide) also induces differentiation of the malignant myeloid clone by dissociating the PML/RAR-alpha-RXR complex from the target genes and was found to have a synergistic action with ATRA [5].
Based on the early French-American-British (FAB) classification, Acute Promyelocytic Leukaemia (APL) is one of the subtypes (M3) of Acute Myeloid Leukemia AML [1]. The PML-RARA fusion is reportedly found in 5-15% of AML and occurs at any age but predominantly in adults in mid-life [1,2]. ''RARA'' fusion proteins behave as potent transcriptional repressors of retinoic acid signaling, inducing a differentiation blockage at the promyelocyte stage which can be overcome with therapeutic doses of all-trans retinoic acid (ATRA) or arsenic trioxide [1-5]. ATO (arsenic trioxide) also induces differentiation of the malignant myeloid clone by dissociating the PML/RAR-alpha-RXR complex from the target genes and was found to have a synergistic action with ATRA [4].
==Gene Overview==
==Gene Overview==
==Common Alteration Types==
==Common Alteration Types==
The translocation involving PML and RARA are found in more than 90% of cases of APL. Other fusion partners to RARA found in APL include PZLF, NPM1, NUMA1, STAT5B and BCOR. These rarer fusion genes account for around 5% of the total found in APL. Patients with these different fusion genes show different clinical responses to ATRA treatment. PZLF-RARA and STAT5b-RARA cases were refractory to ATRA, whereas NPM-RARA and NuMA-RARA were reported to be responsive. BCOR-RARA was also responsive to ATRA but carries a higher risk of relapse [4]
The translocation involving ''PML'' and ''RARA'' are found in more than 90% of cases of APL. Other fusion partners to ''RARA'' found in APL include ''PZLF'', ''NPM1'', ''NUMA1'', ''STAT5B'' and ''BCOR''. These rarer fusion genes account for around 5% of the total found in APL. Patients with these different fusion genes show different clinical responses to ATRA treatment. PZLF-RARA and STAT5b-RARA cases were refractory to ATRA, whereas NPM-RARA and NuMA-RARA were reported to be responsive. BCOR-RARA was also responsive to ATRA but carries a higher risk of relapse [4].
{| class="wikitable sortable"
{| class="wikitable sortable"
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
! Copy Number Loss !! Copy Number Gain !! LOH !! Loss-of-Function Mutation !! Gain-of-Function Mutation !! Translocation/Fusion
|-
|-
| || || || X || || X
| || || || || || X
|}
|}
==Internal Pages==
==Internal Pages==
[http://www.ccga.io/index.php/Acute_Promyelocytic_Leukemia_(APL)_with_PML-RARA Acute Promyelocytic Leukemia (APL) with PML-RARA]
[http://www.ccga.io/index.php/HAEM5:Acute_promyelocytic_leukaemia_with_PML::RARA_fusion Acute Promyelocytic Leukemia (APL) with PML-RARA]
[http://www.ccga.io/index.php/Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
[http://www.ccga.io/index.php/HAEM4:Acute_Myeloid_Leukemia_(AML)_and_Related_Precursor_Neoplasms Acute Myeloid Leukemia (AML) and Related Precursor Neoplasms]
[http://www.ccga.io/index.php/NPM1 NPM1]
[http://www.ccga.io/index.php/NPM1 NPM1]
==References==
==References==
1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.
1. Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. Revised 4th Edition. IARC Press: Lyon, France, p134-136.
2. Schafer, E.S. . et al. (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
2. Schafer ES, et al., (2015). Molecular Genetics of Acute Lymphoblastic Leukemia in The Molecular Basis of Cancer, 4th edition. Mendelsohn, J, Howley, PM, Israel, MA, Gray, JW, Thompson, CB. Editors. Elsevier Press: Philadelphia, USA, p395-406.
3. DeBraekeleer, E. (2014). RARA fusion genes in acute promyelocytic leukemia: a review. Expert Rev Hematol. 7: 347-57. PMID 24720386 DOI: 10.1586/17474086.2014.903794
3. DeBraekeleer E, (2014). RARA fusion genes in acute promyelocytic leukemia: a review. Expert Rev Hematol 7: 347-357, PMID 24720386. DOI: 10.1586/17474086.2014.903794.
4. Ng C.H. and Chng W.J. (2017). Recent advances in acute promyelocytic leukaemia. F1000Res. 6:1273. PMID 28794865 DOI: 10.12688/f1000research.10736.1
4. Ng CH and Chng WJ, (2017). Recent advances in acute promyelocytic leukaemia. F1000Res 6:1273, PMID 28794865. DOI: 10.12688/f1000research.10736.1.
5. Cingam, S. R. and Koshy, N.V. (2017). Cancer, Leukemia, Promyelocytic, Acute (APL, APML). https://www.ncbi.nlm.nih.gov/books/NBK459352/
5. Cingam SR and Koshy NV, (2017). Cancer, Leukemia, Promyelocytic, Acute (APL, APML). https://www.ncbi.nlm.nih.gov/books/NBK459352/.
== Notes ==
== Notes ==